u-75412e and Necrosis

The lazaroid (21-aminosteroid) analogue U75412E was evaluated in rabbits exposed to diesel fuel-polycarbonate plastic smoke. Inhalation of total of 4.6 mg U75412E aerosolized at a rate of 1.53 mg/min for 3 min before or after smoke significantly prevented or limited the extent of alveolar hypoventilation, interstitial edema, and tumor necrosis factor-alpha (TNF-alpha) by pulmonary alveolar macrophages (PAM) ex vivo observed at 2 h. The smoke-induced changes in wet lung/body weight ratios and the production of superoxide (O2-) by PAM ex vivo were also attenuated by the drug treatment after smoke exposure (p < 0.05). This study suggests that lazaroids may ameliorate the oxygen-radical-initiated cytokine processes and inflammation cascade as a result of the smoke insult.

Topics: Analysis of Variance; Animals; Antioxidants; Biological Assay; Disease Models, Animal; Female; Lung; Macrophages, Alveolar; Necrosis; Pulmonary Gas Exchange; Rabbits; Smoke Inhalation Injury; Steroids; Tumor Necrosis Factor-alpha

Free-radical-mediated tissue damage is thought to be involved in a multitude of ophthalmic pathologies. Therefore, drugs that scavenge free radicals may find wide clinical application. A new chemical class of antiinflammatory agents, the 21-aminosteroids, has been developed as free radical scavengers. These agents are thought to inhibit lipid peroxidation and prevent the release of free arachidonic acid from injured cell membranes. In the present study, we investigated the intraocular toxicity of one of the 21-aminosteroids, U75412E. Intravitreal doses of up to 0.1 mg of U75412E were nontoxic to rabbit ocular tissues.

Topics: Animals; Antioxidants; Dark Adaptation; Electroretinography; Free Radical Scavengers; Necrosis; Rabbits; Retina; Steroids; Vitreous Body